A New Synthesis of Protected Phosphonodipeptides with an N-Terminal Amino Acid

A new simple protocol for the direct synthesis of phosphonodipeptides from N-protected amino acids, diethyl 1-azidoalkylphosphonates and tertiary alkyl phosphine (Bu3P, Me3P) was developed. The method is general and the coupling occurred with good yield (42–97%). Depending on the phosphine used and/or mechanism operating during the condensation, the reaction can be accomplished at room temperature, or on heating in toluene.